The long term objectives of this research plan are to apply contemporary electrophysiological and pharmacological techniques to obtain an improved understanding of the mechanisms responsible for atrial flutter and to develop an improved basis for the treatment of atrial flutter. The specific aims of the research plan include the use of the pericarditis canine model of atrial flutter and multiplexing techniques to record simultaneously from 240 electrodes placed on the atrial 1) to characterize the nature of the reentry circuit during atrial flutter; 2) to study the nature of conduction in the center of the atrial flutter reentry circuit; 3) to characterize fully transient entrainment and interruption of atrial flutter; 4) to utilize rapid atrial pacing during sinus rhythm and during atrial flutter (entrainment) to characterize conduction in tissues that constitute the atrial flutter reentry circuit in the right atrium; 5) to characterize conduction at pivot points of activation wave fronts; 6) to study how antiarrhythmic and other selected agents act on the atrial flutter reentry circuit; 7) to test the efficacy of selected interventions for the prevention of inducibility of atrial flutter. The studies will address 15 hypotheses concerned with the maintenance of atrial flutter, the treatment of atrial flutter, and the prevention of atrial flutter. The methods to be used to further characterize and study atrial flutter in this canine model include the use of aseptic surgery to create the sterile pericarditis canine model, the use of standard surgical techniques to expose the heart again following creation of chronic sterile pericarditis; the use of multiplex recording techniques during the various electrophysiologic studies; the use of cardiac pacing techniques; and the use of standard pharmacological techniques for the administration of selected agents. The health relatedness of the project is clear, in that atrial flutter is a well known, clinically troublesome, and poorly understood abnormality affecting patients in significant numbers. The proposed studies should provide important new information to assist in improved understanding and treatment of patients suffering from this abnormality.